Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD, Neuhaus J, Phillips AN.Collaborators (750)Gordin F, Finley E, Dietz D, Chesson C, Vjecha M, Standridge B, Schmetter B, Grue L, Willoughby M, Demers A, Lundgren JD, Phillips A, Dragsted UB, Jensen KB, Fau A, Borup L, Pearson M, Jansson PO, Jensen BG, Benfield TL, Darbyshire JH, Babiker AG, Palfreeman AJ, Fleck SL, Collaco-Moraes Y, Cordwell B, Dodds W, van Hoff F, Wazydrag L, Cooper DA, Emery S, Drummond FM, Connor SA, Satchell CS, Gunn S, Oka S, Delfino MA, Merlin K, McGinley C, Neaton JD, DuChene A, Harrison M, George M, Grund B, Hogan C, Krum E, Larson G, Miller C, Nelson R, Neuhaus J, Roediger MP, Schultz T, Thackeray L, Prineas R, Campbell C, Perez G, Lifson A, Duprez D, Hoy J, Lahart C, Perlman D, Price R, Prineas R, Rhame F, Sampson J, Worley J, Rein M, DerSimonian R, Brody BA, Daar ES, Dubler NN, Fleming TR, Freeman DJ, Kahn JP, Kim KM, Medoff G, Modlin JF, Moellering R Jr, Murray BE, Pick B, Robb ML, Scharfstein DO, Sugarman J, Tsiatis A, Tuazon C, Zoloth L, Klingman K, Lehrman S, Lazovski J, Belloso WH, Losso MH, Benetucci JA, Aquilia S, Bittar V, Bogdanowicz EP, Cahn PE, Casiró AD, Cassetti I, Contarelli JM, Corral JA, Crinejo A, Daciuk L, David DO, Guaragna G, Ishida MT, Krolewiecki A, Laplume HE, Lasala MB, Lourtau L, Lupo SH, Maranzana A, Masciottra F, Michaan M, Ruggieri L, Salazar E, Sánchez M, Somenzini C, Hoy JF, Rogers GD, Allworth AM, Anderson JS, Armishaw J, Barnes K, Carr A, Chiam A, Chuah JC, Curry MC, Dever RL, Donohue WA, Doong NC, Dwyer DE, Dyer J, Eu B, Ferguson VW, French MA, Garsia RJ, Gold J, Hudson JH, Jeganathan S, Konecny P, Leung J, McCormack CL, McMurchie M, Medland N, Moore RJ, Moussa MB, Orth D, Piper M, Read T, Roney JJ, Roth N, Shaw DR, Silvers J, Smith DJ, Street AC, Vale RJ, Wendt NA, Wood H, Youds DW, Zillman J, Rieger A, Tozeau V, Aichelburg A, Vetter N, Clumeck N, Dewit S, de Roo A, Kabeya K, Leonard P, Lynen L, Moutschen M, O'Doherty E, Pereira C Jr, Souza TN, Schechter M, Zajdenverg R, Almeida MM, Araujo F, Bahia F, Brites C, Caseiro MM, Casseb J, Etzel A, Falco GG, Filho EC, Flint SR, Gonzales CR, Madruga JV, Passos LN, Reuter T, Sidi LC, Toscano AL, Zarowny D, Cherban E, Cohen J, Conwa B, Dufour C, Ellis M, Foster A, Haase D, Haldane H, Houde M, Kato C, Klein M, Lessard B, Martel A, Martel C, McFarland N, Paradis E, Piche A, Sandre R, Schlech W, Schmidt S, Smaill F, Thompson B, Trottier S, Vezina S, Walmsley S, Wolff Reyes MJ, Northland R, Ostergaard L, Pedersen C, Nielsen H, Hergens L, Loftheim IR, Jensen KB, Raukas M, Zilmer K, Justinen J, Ristola M, Girard PM, Landman R, Abel S, Abgrall S, Amat K, Auperin L, Barruet R, Benalycherif A, Benammar N, Bensalem M, Bentata M, Besnier JM, Blanc M, Bouchaud O, Cabié A, Chavannet P, Chennebault JM, Dargere S, de la Tribonniere X, Debord T, Decaux N, Delgado J, Dupon M, Durant J, Frixon-Marin V, Genet C, Gérard L, Gilquin J, Hoen B, Jeantils V, Kouadio H, Leclercq P, Lelièvre JD, Levy Y, Michon CP, Nau P, Pacanowski J, Piketty C, Poizot-Martin I, Raymond I, Salmon D, Schmit JL, Serini MA, Simon A, Tassi S, Touam F, Verdon R, Weinbreck P, Weiss L, Yazdanpanah Y, Yeni P, Fätkenheuer G, Staszewski S, Bergmann F, Bitsch S, Bogner JR, Brockmeyer N, Esser S, Goebel FD, Hartmann M, Klinker H, Lehmann C, Lennemann T, Plettenberg A, Potthof A, Rockstroh J, Ross B, Stoehr A, Wasmuth JC, Wiedemeyer K, Winzer R, Hatzakis A, Touloumi G, Antoniadou A, Daikos GL, Dimitrakaki A, Gargalianos-Kakolyris P, Giannaris M, Karafoulidou A, Katsambas A, Katsarou O, Kontos AN, Kordossis T, Lazanas MK, Panagopoulos P, Panos G, Paparizos V, Papastamopoulos V, Petrikkos G, Sambatakou H, Skoutelis A, Tsogas N, Xylomenos G, Bergin CJ, Mooka B, Pollack S, Mamorksy MG, Agmon-Levin N, Karplus R, Kedem E, Maayan S, Shahar E, Sthoeger Z, Turner D, Yust I, Tambussi G, Rusconi V, Abeli C, Bechi M, Biglino A, Bonora S, Butini L, Carosi G, Casari S, Corpolongo A, De Gioanni M, Di Perri G, Di Pietro M, D'Offiz G, Esposito R, Mazzotta F, Montroni M, Nardini G, Nozza S, Quirino T, Raise E, Honda M, Ishisaka M, Caplinskas S, Uzdaviniene V, Schmit JC, Staub T, Himmich H, Marhoum El Filali K, Mills GD, Blackmore T, Masters JA, Morgan J, Pithie A, Brunn J, Ormasse V, La Rosa A, Guerra O, Espichan M, Gutierrez L, Mendo F, Salazar R, Knytz B, Horban A, Bakowska E, Beniowski M, Gasiorowski J, Kwiatkowski J, Antunes F, Castro RS, Doroana M, Horta A, Mansinho K, Miranda AC, Pinto IV, Valadas E, Vera J, Rakhmanova A, Vinogradova E, Yakovlev A, Zakharova N, Wood R, Orrel C, Gatell J, Arnaiz JA, Carrillo R, Clotet B, Dalmau D, González A, Jordano Q, Jou A, Knobel H, Larrousse M, Mata R, Moreno JS, Oretaga E, Pena JN, Pulido F, Rubio R, Sanz J, Viciana P, Hirschel B, Spycher R, Battegay M, Bernasconi E, Bottone S, Cavassini M, Christen A, Franc C, Furrer HJ, Gayet-Ageron A, Genné D, Hochstrasser S, Magenta L, Moens C, Müller N, Nüesch R, Phanuphak P, Ruxrungtham K, Pumpradit W, Chetchotisakd P, Dangthongdee S, Kiertiburanakul S, Klinbuayaem V, Mootsikapun P, Nonenoy S, Piyavong B, Prasithsirikul W, Raksakulkarn P, Gazzard BG, Ainsworth JG, Anderson J, Angus BJ, Barber TJ, Brook MG, Care CD, Chadwick DR, Chikohora M, Churchill DR, Cornforth D, Dockrell DH, Easterbrook PJ, Fox PA, Fox R, Gomez PA, Gompels MM, Harris GM, Herman S, Jackson AG, Jebakumar SP, Johnson MA, Kinghorn GR, Kuldanek KA, Larbalestier N, Leen C, Lumsden M, Maher T, Mantell J, Maw R, McKernan S, McLean L, Morris S, Muromba L, Orkin CM, Palfreeman AJ, Peters BS, Peto TE, Portsmouth SD, Rajamanoharan S, Ronan A, Schwenk A, Slinn MA, Stroud CJ, Thomas RC, Wansbrough-Jones MH, Whiles HJ, White DJ, Williams E, Williams IG, Youle M, Abrams I, Acosta EA, Adams S, Adamski A, Andrews L, Antoniskis D, Aragon DR, Arduino R, Artz R, Bailowitz J, Barnett BJ, Baroni C, Barron M, Baxter JD, Beers D, Beilke M, Bemenderfer D, Bernard A, Besch CL, Bessesen MT, Bethel JT, Blue S, Blum JD, Boarden S, Bolan RK, Borgman JB, Brar I, Braxton BK, Bredeek UF, Brennan R, Britt DE, Brockelman J, Brown S, Bruzzese V, Bulgin-Coleman D, Bullock DE, Cafaro V, Campbell B, Caras S, Carroll J, Casey KK, Chiang F, Childress G, Cindrich RB, Clark C, Climo M, Cohen C, Coley J, Condoluci DV, Contreras R, Corser J, Cozzolino J, Crane LR, Daley L, Dandridge D, D'Antuono V, Darcourt Rizo Patron JG, DeHovitz JA, DeJesus E, DesJardin J, Diaz-Linares M, Dietrich C, Dodson P, Dolce E, Elliott K, Erickson D, Estes M, Faber LL, Falbo J, Farrough MJ, Farthing CF, Ferrell-Gonzalez P, Flynn H, Frank C, Frank M, Freeman KF, French N, Friedland G, Fujita N, Gahagan L, Genther K, Gilson I, Goetz MB, Goodwin E, Graziano F, Guity CK, Gulick P, Gunderson ER, Hale CM, Hannah K, Henderson H, Hennessey K, Henry WK, Higgins DT, Hodder SL, Horowitz HW, Howe-Pittman M, Hubbard J, Hudson R, Hunter H, Hutelmyer C, Insignares MT, Jackson L, Jenny L, John M, Johnson DL, Johnson G, Johnson J, Johnson L, Kaatz J, Kaczmarski J, Kagan S, Kantor C, Kempner T, Kieckhaus K, Kimmel N, Klaus BM, Klimas N, Koeppe JR, Koirala J, Kopka J, Kostman JR, Kozal MJ, Kumar A, Labriola A, Lampiris H, Lamprecht C, Lattanzi KM, Lee J, Leggett J, Long C, Loquere A, Loveless K, Lucasti CJ, Luskin-Hawk R, MacVeigh M, Makohon LH, Mannheimer S, Markowitz NP, Marks C, Martinez N, Martorell C, McFeaters E, McGee B, McIntyre DM, McKee J, McManus E, Melecio LG, Melton D, Mercado S, Merrifield E, Mieras JA, Mogyoros M, Moran FM, Murphy K, Mushatt D, Mutic S, Nadeem I, Nadler JP, Nahass R, Nixon D, O'Brien S, Ognjan A, O'Hearn M, O'Keefe K, Okhuysen PC, Oldfield E, Olson D, Orenstein R, Ortiz R, Osterberger J, Owen W, Parpart F, Pastore-Lange V, Paul S, Pavlatos A, Pearce DD, Pelz R, Perez G, Peterson S, Pierone G Jr, Pitrak D, Powers SL, Pujet HC, Raaum JW, Ravishankar J, Reeder J, Regevik N, Reilly NA, Reyelt C, Riddell J 4th, Rimland D, Robinson ML, Rodriguez AE, Rodriguez-Barradas MC, Rodriguez Derouen V, Roland R, Rosmarin C, Rossen WL, Rouff JR, Sampson JH, Sands M, Savini C, Schrader S, Schulte MM, Scott C, Scott R, Seedhom H, Sension M, Sheble-Hall A, Sheridan A, Shuter J, Slater LN, Slotten R, Slowinski D, Smith M, Snap S, States DM, Stewart M, Stringer G, Sullivan J, Summers KK, Swanson K, Sweeton IB, Szabo S, Tedaldi EM, Telzak EE, Temesgen Z, Thomas D, Thompson MA, Thompson S, Ting Hong Bong C, Tobin C, Uy J, Vaccaro A, Vasco LM, Vecino I, Verlinghieri GK, Visnegarwala F, Wade BH, Watson V, Weis SE, Weise JA, Weissman S, Wilkin AM, Williams L, Witter JH, Wojtusic L, Wright TJ, Yeh V, Young B, Zeana C, Zeh J, Savio E, Vacarezza M.
Copenhagen HIV Programme (CHIP), Faculty of Health Sciences, University of Copenhagen, Panum Institute, 2200 Copenhagen N, Denmark. jdl@cphiv.dk
BACKGROUND AND METHODS: The SMART study compared 2 strategies for using antiretroviral therapy-drug conservation (DC) and viral suppression (VS)-in 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. RESULTS: During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/microL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow- up with a CD4+ cell count <350 cells/microL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95% confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count >or= 350 cells/microL-an increase explained by the higher HIV RNA levels in the DC group. CONCLUSIONS: The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death.
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PMID: 18476293 [PubMed - indexed for MEDLINE]